Correlation of serum C1q-tumour necrosis factor-related protein 5 levels with metabolic parameters and carotid intima-media thickness in newly diagnosed type 2 diabetes mellitus patients.

PURPOSE: Recent studies have shown that cytokines secreted from adipose tissues play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). CTRP5 (C1q-TNF-related protein 5) is a novel adipokine that has been shown to be associated with glucose and lipid metabolism. Varying levels of CTRP5 have been reported in individuals with diabetes, obesity and coronary artery disease. The aim of this study was to examine serum levels of CTRP5 and to show the relationship with cardiometabolic parameters in T2DM patients. METHOD: The study included 40 T2DM patients and 40 age- and sex-matched healthy control subjects. All the study participants were evaluated with respect to BMI, waist circumference, lipid profile, insulin resistance (HOMA-IR), serum CTRP5 levels, carotid intima-media thickness, and hs-CRP. RESULTS: No statistically significant differences were found between the control group and the diabetic group in terms of age, sex, or BMI. Serum CTRP5 levels (T2DM = 94.55 ± 28.70 ng/ml, control = 76.02 ± 27.22 ng/ml, P = 0.004*) were significantly higher in the group of newly diagnosed diabetic patients. A positive correlation was found between CTRP5 and the cardiometabolic parameters of carotid intima-media thickness (CIMT), hs-CRP, HOMA-IR and BMI. Regression analysis results showed that CTRP5 levels were independently correlated with insulin resistance estimated by HOMA-IR. CONCLUSION: Serum CTRP5 levels were correlated with cardiometabolic parameters and could therefore be a promising indicator of metabolic status and a possible biomarker of insulin resistance. However, the contradictory results reported in different studies indicate the need for further research to assess the significance of CTRP5 for diagnosis and monitoring of treatment efficacy.

Neudesin: a neuropeptide hormone decreased in subjects with polycystic ovary syndrome.

Neudesin is a neuropeptide hormone involves in female reproduction system via promoting effects of progesterone. Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disorder associated with hypothalamic-pituitary-ovarian axis abnormalities and impaired negative feedback mechanism of progesterone upon gonadotropin-releasing hormone secretion. Our aims were to discover whether neudesin levels were altered in PCOS women comparing to controls and to determine the link of neudesin with hormonal-metabolic parameters in PCOS women. The current research was designed as a case-control study. Sixty-eight subjects with PCOS and 67 age- and body mass index (BMI)-matched subjects as controls were enrolled into the study. Circulating neudesin levels were measured by ELISA. Neudesin levels were significantly lower in PCOS subjects compared to controls (4.07 ± 1.22 vs. 6.02 ± 2.07 ng/ml, p < .001). Neudesin exhibited an inversely independent link with luteinizing hormone, free-androgen index, and BMI whereas it showed a positively independent link with progesterone in women with PCOS. Logistic regression analysis revealed that decreased neudesin levels were parallel with increased risk of having PCOS. Decreased neudesin levels were associated with hormonal disturbances in PCOS women, suggesting that neudesin may play a role in pathophysiology of PCOS.

Fractalkine: an inflammatory chemokine elevated in subjects with polycystic ovary syndrome.

PURPOSE: Fractalkine (FKN) is an inflammatory chemokine related to reproductive system and glucose metabolism. There is a link between FKN and steroidogenesis as FKN induces progesterone synthesis. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with low progesterone production and insulin resistance. We aimed to explore whether women with PCOS have any difference in FKN levels compared to women without PCOS. We also focused on determination of any association between FKN levels and hormonal-metabolic parameters in women with PCOS. METHODS: The current research was designed as a case-control study. Eighty subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle were taken into the study. We measured circulating FKN levels via ELISA methods. RESULTS: Circulating FKN levels were higher in women with PCOS than controls (1.93 ± 0.61 vs. 1.22 ± 0.33 ng/ml, P< 0.001). FKN levels showed a positive correlation with body mass index (BMI), insulin resistance, inflammatory marker hs-CRP, total testosterone, and free-androgen index (FAI), whereas it showed a negative correlation with sex hormone-binding protein in women with PCOS. Linear regression analyses revealed that the link of FKN with BMI, insulin resistance, hs-CRP, and FAI was independent. Binary logistic regression analysis showed that the risk of having PCOS was associated with high levels of FKN. CONCLUSIONS: Increased FKN levels related to insulin resistance, inflammation and androgens in women with PCOS. FKN may have an inter-related role in different pathophysiologic pathways of PCOS.

Circulating insulin-like peptide 5 levels and its association with metabolic and hormonal parameters in women with polycystic ovary syndrome.

PURPOSE: Insulin-like peptide 5 (INSL5) is a gut peptide hormone that is a member of relaxin/insulin superfamily. Growing evidence implicates the crucial role of the peptide in some metabolisms including food intake, glucose homeostasis and reproductive system. Polycystic ovary syndrome (PCOS) is involved in both reproductive and metabolic issues. The aim of the study was determination of circulating levels of INSL5 alteration in women with PCOS and evaluation of the relationship between INSL5 and hormonal-metabolic parameters as well as carotid intima media thickness (cIMT). METHODS: A total of 164 subjects were recruited in this cross-sectional study (82 women with PCOS and 82 age- and BMI-matched controls). Circulating INSL5 levels were assessed via ELISA method. High-resolution B-mode ultrasound was used to measure cIMT. The hormonal and metabolic parameters of the recruited subjects were determined. RESULTS: Circulating INSL5 levels were significantly elevated in women with PCOS compared to controls (27.63 ± 7.74 vs. 19.90 ± 5.85 ng/ml, P < 0.001). The mean values of INSL5 were significantly higher in overweight subjects compared to lean weight subjects in both groups. The women with PCOS having insulin resistance have increased INSL5 compared to those of PCOS subjects without insulin resistance. INSL5 is associated with insulin resistance, BMI, luteinizing hormone and free androgen index. Multivariate logistic regression analyses revealed that the odds ratio for having PCOS in the highest tertile of INSL5 was higher than in the lowest tertile. CONCLUSIONS: PCOS subjects exhibited an elevation in circulating INSL5 levels along with a link between INSL5 level induction and metabolic-hormonal parameters.

Association of decreased C1q/tumor necrosis factor-related protein-5 levels with metabolic and hormonal disturbance in polycystic ovary syndrome

Objective: C1q/tumor necrosis factor-related protein-5 (CTRP5) is a novel peptide hormone involved in the metabolism of energy regulation. Polycystic ovary syndrome (PCOS), which is a reproductive and metabolic disorder, is associated with insulin resistance. The aim of the current study was to compare circulating levels of CTRP5 in women with and without PCOS and to investigate possible associations between CTRP5 and metabolic-hormonal parameters. Material and Methods: The present cross-sectional study contained 80 women with PCOS and 80 age and body mass index-matched women without PCOS. Circulating levels of CTRP5 were calculated using an enzyme-linked immunosorbent assay. We also measured hormonal and metabolic parameters. Results: Patients with PCOS had lower levels of circulating CTRP5 compared with women without PCOS (6.90±2.64 vs 11.73±3.66 ng/mL, p<0.001). CTRP5 was negatively correlated with insulin resistance, free-androgen index, and body mass index in both the PCOS and control groups. Moreover, patients with PCOS who had insulin resistance showed lower circulating CTRP5 levels compared with those without insulin resistance. In both the control and PCOS groups, overweight subjects had lower circulating levels of CTRP5 compared with participants of normal weight. Logistic regression analyses indicated that subjects in the lowest tertile for CTRP5 level had higher risk for PCOS compared with those in the highest tertile of CTRP5. Conclusion: Decreased circulating levels of CTRP5 were associated with higher risk of PCOS, as well as having metabolic disturbance among women with PCOS.

The prevalence and systemic risk factors of diabetic macular edema: a cross-sectional study from Turkey.

BACKGROUND: The aim of this study was to evaluate the prevalence of diabetic macular edema (DME) utilizing optical coherence tomography (OCT), and to clarify the effects of the systemic findings and risk factors on the development of DME. METHODS: This cross-sectional study was conducted in the departments of ophthalmology and endocrinology at the Dokuz Eylul University School of Medicine in Izmir, Turkey. The demographics, type and duration of diabetes mellitus, treatment modality, smoking and alcohol consumption habits, as well as the systemic blood pressure, renal functional tests, hemoglobulin A1c level, serum lipid profile, and 24-h urine albumin level were noted and statistically analyzed. The relationships between the systemic findings and DME were studied. RESULTS: Four-hundred and thirteen eyes of 413 diabetic patients who were examined between January 2011 and July 2012 were enrolled in this study. The prevalence of DME was 15.3% among the patients. The males exhibited DME significantly more frequently than the females (p = 0.031), and the duration of diabetes was significantly longer in those patients with DME (p < 0.001). Those patients without DME frequently used antihyperlipidemic drugs and had a higher level of high density lipoprotein cholesterol (p = 0.040 and p = 0.046, respectively). The patient's alcohol consumption, nephropathy, neuropathy, previous cataract surgery, severity of diabetic retinopathy, and insulin usage were statistically significant factors with regard to the DME prevalence. CONCLUSIONS: This study demonstrated the prevalence of DME in Turkey by utilizing OCT. The development of DME can be avoided or limited and the response to treatment may be improved by the regulation of the DME risk factors.

Association of kallistatin with carotid intima-media thickness in women with polycystic ovary syndrome.

BACKGROUND: Kallistatin is a secreted protein that acts as a tissue kallikrein inhibitor. It has anti-inflammatory, antioxidant and vasoprotective properties. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with low-grade chronic inflammation and multiple risk factors for cardiovascular diseases. The aims of this study were to ascertain whether circulating kallistatin levels are altered in women with PCOS, and whether there is an association between kallistatin and carotid intima-media thickness (cIMT) as well as inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α). METHODS: This cross-sectional study included 75 women with PCOS and 75 age- and BMI-matched controls without PCOS. Circulating kallistatin and TNF-α levels were measured using ELISA. Metabolic and hormonal parameters, hs-CRP levels and cIMT were also determined. All subjects underwent the 2-hour oral glucose tolerance test (2-h OGTT). RESULTS: Circulating kallistatin levels were significantly elevated in women with PCOS compared to controls (6.31±2.09 vs. 4.79±2.26 ng/mL, P<0.001). Inflammatory markers hs-CRP and TNF-α were found to be elevated in women with PCOS. Kallistatin levels positively correlated with insulin, insulin resistance index (HOMA-IR), free androgen index, hs-CRP, TNF-α and cIMT in both PCOS and control groups. Kallistatin levels did not show correlation with BMI, blood pressure, fasting blood glucose, 2-h OGTT or HbA1c. Multiple linear regression analysis revealed that kallistatin is an independent predictor for cIMT (ß=0.131, 95% CI: 0.114-0.150, P=0.019). CONCLUSIONS: Kallistatin levels may provide useful information regarding cardiovascular risk in women with PCOS.

Relationship between insulin resistance, hs-CRP, and body fat and serum osteoprotegerin/RANKL in prediabetic patients.

BACKGROUND: Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPN) are soluble members of the tumor necrosis factor superfamily. Growing evidence suggest that there is link between inflammation, insulin resistance and OPG, soluble RANKL (sRANKL). We aimed to ascertain whether OPG and sRANKL levels are altered in prediabetic subjects and there is association between OPG/sRANKL and metabolic parameters. METHODS: Forty prediabetic subjects and 40 age- and BMI-matched controls were recruited for this cross-sectional study. Circulating OPG, sRANKL were measured using ELISA. Anthropometric and metabolic parameters were also determined. RESULTS: Circulating sRANKL (97.74±17.67 vs. 55.00±11.19 pg/mL, P=0.010) and OPG (261.54±74.55 vs. 159.23±52.91 pg/mL, P=0.020) levels were found to be significantly higher in diabetic subjects compared with control subjects. There was a positive correlation between sRANKL and OPG. sRANKL also positively correlated with BMI, insulin resistance marker HOMA-IR, inflammatory marker hs-CRP. Logistic regression analyses revealed that the odds ratio was increased for prediabetes in subjects with having elevated sRANKL levels. CONCLUSIONS: Increased sRANKL and OPG levels were associated with prediabetic subjects. sRANKL and OPG may play a role in the pathogenesis of diabetes as well as metabolic disturbance.

Increased serum neuregulin 4 levels in women with polycystic ovary syndrome: A case-control study.

Neuregulin 4 (NRG4) is an adipokine that is synthesized in many tissues and has been shown to be associated with the development of obesity and metabolic disorders in animals and humans. The aim of this study is to investigate the relationship between serum NRG4 levels and various metabolic parameters in women with PCOS. This cross-sectional study included 40 women with PCOS and 40 age- and BMI-matched controls without PCOS. NRG4, fasting blood glucose (FBG), insulin, hs-CRP, LDL-C, HDL-C, SHBG, DHEA-SO4 and total-testosterone levels were measured in all the participants. HOMA-IR was used to calculate the insulin resistance. Serum NRG4 levels were higher in women with PCOS than in healthy women (24.89 ± 9.32 [ng/mL] vs. 18.98 ± 6.40 [ng/mL], p = 0.002). FBG, LDL-C, HDL-C, LH, SHBG, FAI, DHEA-SO4, insulin, hs-CRP, HOMA-IR and total-testosterone levels were significantly higher in women with PCOS than controls. Circulating NRG4 levels were positively correlated with HOMA-IR, insulin and hs-CRP for both groups. There was a positive correlation between NRG4 and FBG in the PCOS group. HOMA-IR and hs-CRP were associated with NRG4. The high concentration of circulating NRG4 in PCOS may be associated with insulin resistance and low-grade chronic inflammation.

Elevated circulating levels of xenopsin-related peptide-1 are associated with polycystic ovary syndrome.

PURPOSE: This study was conducted to compare serum xenopsin-related peptide-1 (XP-1) levels in women with polycystic ovary syndrome (PCOS) and in healthy women and to determine the role of XP-1 levels in PCOS. METHODS: Forty patients with PCOS and 38 healthy women were included in the study and matched with age and body mass index. Fasting blood glucose, insulin, high sensitivity C-reactive protein (hs-CRP), XP-1 and total testosterone levels of all participants were measured. RESULTS: Serum XP-1 levels significantly increased in women with PCOS compared to the control group (6.49 ± 1.57 vs 5.29 ± 1.45 ng/ml, p = 0.001). Serum insulin, hs-CRP, HOMA-IR, total testosterone levels and waist circumference were higher in women with PCOS than in control group. High XP-1 levels were associated with PCOS after adjustment for potential confounders. Receiver operating characteristic (ROC) curve analysis confirmed that the area under ROC curves was 0.703 (95% CI 0.588-0.818, p < 0.002) for XP-1 levels. The optimal cut-off value of XP-1 for detecting PCOS was ≥5.87 ng/ml. CONCLUSIONS: Our results indicate that increased XP-1 levels were associated with PCOS after adjustment for potential confounders, which has been shown to be effective in the function of the insulin signaling pathway.

The relationship between lipocalin-2 and free testosterone levels in polycystic ovary syndrome.

INTRODUCTION: Lipocalin-2 is an adipokine that is mainly produced from adipocytes and macrophages. Data related to PCOS and other obesity-associated disorders have shown divergent results. Here, we studied lipocalin-2 concentrations in women with PCOS and in healthy women, and investigated the potential contributors underlying lipocalin association with PCOS. MATERIAL AND METHODS: Forty-four women with PCOS and 47 age- and BMI-matched healthy women were enrolled. Fasting serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP), and free testosterone levels were measured. The body fat percentage was measured by bioelectrical impedance. RESULTS: Lipocalin-2 concentrations were significantly higher in the PCOS group than in the control group (55.74 ± 17.54 ng/mL vs. 36.46 ± 19.62 ng/mL, p = 0.011). There was a correlation between lipocalin-2 levels and free testosterone. In a multiple regression model, the body fat percentage, HOMA-IR, and hs-CRP were not associated with lipocalin-2. However, only free testosterone was associated with lipocalin-2. A "lipocalin-2 = 11.214 + (1.943 × free-testosterone)" equation was obtained. CONCLUSIONS: Serum lipocalin-2 levels were higher in women with PCOS, and only free testosterone was associated with lipocalin-2. Lipocalin-2 levels and their influencing factors have discrepant results in both PCOS and other obesity- or insulin resistance-related metabolic disorders. Thus, the potential role of lipocalin-2 in PCOS should be clarified. (Endokrynol Pol 2017; 68 (1): 7-12).

The relationship of urocortin-2 with insulin resistance patients having PCOS.

In this study, we aimed to compare the serum urocortin-2 (UCN2) levels in women with polycystic ovary syndrome (PCOS) and healthy women. Thirty-eight patients with PCOS and 41 healthy women were included in the study whose age and BMI matched. The fasting serum glucose, insulin, free testosterone, hs-CRP and UCN2 levels of the all participants were examined. HOMA-IR formula was used in order to calculate the insulin resistance. Circulating UCN2 levels were significantly elevated in women with PCOS compared with controls (142.93 ± 59.48 versus 98.56 ± 65.01 pg/ml, p = 0.002). FBG, serum insulin, hs-CRP and HOMA-IR levels were found to be increased in women with PCOS. There was a positive correlation between UCN2 and free-testosterone in only PCOS group (r = 0.235, p = 0.027). Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.31 for patients in the highest quartile of UCN2 compared with those in the lowest quartile (OR = 2.31, 95% CI = 1.88-2.83, p=0.021). Multiple linear regression analysis revealed that HOMA-IR, hs-CRP and free-testosterone independently predicted UCN2 levels (p < 0.05). UCN2 levels were significantly higher in PCOS cases when compared to control group. UCN2 is thought to be effective on pathophysiology of PCOS by paracrine and autocrine pathways.

Evaluation of Meibomian Gland Dysfunction in Polycystic Ovary Syndrome and Obesity.

Purpose/Aim of the study: The purpose of this study was to evaluate the interaction between Polycystic ovary syndrome (PCOS) and Meibomian gland dysfunction (MGD) and obesity, to reveal whether there is a correlation between the testosterone levels and body-mass index (BMI) levels and the dry-eye complaints of these patients. MATERIAL AND METHODS: The study included 92 patients with PCOS and 52 healthy patients from March 2013 to March 2014. All patients underwent a physical examination, pelvic ultrasound, and clinical and biochemical tests, including free testosterone levels to confirm the diagnosis of PCOS. The BMIs of all subjects were recorded. In addition, the presence of posterior blepharitis, as an indicator of MGD, was recorded. All patients underwent the dry-eye tests including Schirmer 1 and tear film break-up time (BUT). Complaints of dry-eye of the patients were evaluated with the ocular surface disease index (OSDI) questionnaire. The scores of both groups were compared. RESULTS: The presence of MGD was 72.82% in the PCOS group and 61.53% in the control group. There was no correlation between the testosterone levels and study parameters in both groups. BUT levels negatively correlated with BMI in subjects without PCOS (r = -0.520, p = 0.001), whereas positively correlated with MGD and OSDI scores (r = 0.610, p = 0.632; p = 0.001, p = 0.001; respectively). CONCLUSION: Tear film instability due to MGD is common in PCOS and in subjects with high BMI. The MGD in PCOS patients is independent of the BMI.

Endocan is a predictor of increased cardiovascular risk in women with polycystic ovary syndrome.

PURPOSE: Endocan is a proteoglycan secreted mainly from endothelial cells. It has been implicated that there is a link between endocan and endothelial dysfunction. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with increased risk of cardiovascular events. The aims of this study were to ascertain whether circulating endocan levels are altered in women with PCOS, and whether there is an association between endocan and carotid intima media thickness (cIMT). MATERIALS AND METHODS: This cross-sectional study included 80 women with PCOS and 80 age- and BMI-matched controls without PCOS. Circulating endocan levels were measured using ELISA. Metabolic, hormonal parameters and cIMT were determined. 2-h oral glucose tolerance test (2-h OGTT) was performed on all women. RESULTS: Circulating endocan levels were significantly elevated in women with PCOS compared with controls (5.99 ± 2.37 vs. 3.66 ± 1.79 ng/ml, P < 0.001). Endocan levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free androgen index (FAI), high-sensitivity C-reactive protein (hs-CRP), and cIMT in both PCOS and control groups. Endocan levels did not correlate with fasting blood glucose, 2-h OGTT, A1C and lipid parameters. Multiple linear regression analysis revealed that endocan is an independent predictor for cIMT (ß = 0.128, 95% CI = 0.118-0.138, P = 0.011). CONCLUSIONS: Circulating endocan levels are significantly higher in women with PCOS and endocan is independently associated with cIMT. Elevated endocan levels can be a predictor of increased cardiovascular risk in PCOS subjects.

Increased adipsin is associated with carotid intima media thickness and metabolic disturbances in polycystic ovary syndrome.

CONTEXT: Adipsin, a protein secreted mainly from the adipose tissue, is a structural homologous of complement factor D, a rate-limiting enzyme of the alternative complement system. Growing evidence suggests that the alternative complement system plays a role both in the regulation of energy homoeostasis and in the atherosclerosis. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease. OBJECTIVE: To ascertain whether circulating adipsin levels are altered in women with PCOS, and whether there is an association between adipsin and metabolic parameters or carotid intima media thickness (CIMT). PARTICIPANTS: A total of 144 women with PCOS and 144 age- and BMI-matched controls without PCOS were recruited for this cross-sectional study. MAIN OUTCOME MEASURES: Circulating adipsin levels were measured using ELISA. Metabolic, hormonal parameters and CIMT were also determined. RESULTS: Adipsin levels were significantly elevated in women with PCOS compared with controls (91·52 ± 14·11 vs 60·31 ± 9·71 ng/ml, P < 0·001). Adipsin positively correlated with BMI, homoeostasis model assessment of insulin resistance (HOMA-IR), free testosterone, high-sensitivity C-reactive protein (hs-CRP) and CIMT in both groups. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 3·25 for patients in the highest quartile of adipsin compared with those in the lowest quartile (OR=3·25, 95% CI=2·64-4·00, P = 0·016). Our findings further indicate that BMI, HOMA-IR, hs-CRP and free testosterone are independent factors influencing serum adipsin levels and that adipsin is an independent predictor for CIMT. CONCLUSION: Circulating adipsin levels are significantly higher in women with PCOS, and the peptide is closely related to increased cardiovascular risk and metabolic disturbances.

A possible link between luteinizing hormone and macrophage migration inhibitory factor levels in polycystic ovary syndrome.

PURPOSE: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that plays a role in metabolic and inflammatory processes. Increasing evidence suggests that there is a link between MIF and ovulation. We aimed to evaluate plasma MIF levels in women with polycystic ovary syndrome (PCOS) and to determine whether MIF levels differ between the follicular phase and mid-cycle of the menstrual cycle in eumenorrheic women. METHODS: Ninety women with PCOS and 80 age- and BMI-matched healthy eumenorrheic women were consecutively recruited into this prospective observational study. For all subjects, plasma MIF levels in the early follicular phase were measured by ELISA; for the 40 healthy controls, MIF levels were also measured during mid-cycle of the same menstrual cycle. RESULTS: Plasma MIF levels were significantly higher in women with PCOS than in eumenorrheic women (14.16 ± 1.59 vs. 10.39 ± 0.70 ng/ml; p < 0.001). MIF levels were significantly higher at mid-cycle than in the follicular phase in eumenorrheic women (11.15 ± 0.61 vs. 10.56 ± 0.82 ng/ml; p < 0.001). MIF was positively correlated with BMI, high sensitivity C-reactive protein (hs-CRP), and homeostasis model assessment of insulin resistance (HOMA-IR) in both groups. MIF was positively correlated with luteinizing hormone (LH) and free-testosterone only in the PCOS group. Binary logistic regression analyses revealed that the odds ratio (OR) for PCOS independently increases linearly with elevated MIF (OR = 1.385, 95% CI = 1.087-1.764, p = 0.017). CONCLUSION: MIF may play a crucial role in the reproductive system in women, including the development of PCOS and normal ovulation.

Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome.

Betatrophin is a newly identified hormone determined to be a potent inducer of pancreatic beta cell proliferation in response to insulin resistance in mice. Polycystic ovary syndrome (PCOS) is an inflammatory-based metabolic disease associated with insulin resistance. However, no evidence is available indicating whether betatrophin is involved in women with PCOS. The objective of this study was to ascertain whether betatrophin levels are altered in women with PCOS. This study was conducted in secondary referral center. This cross-sectional study included 164 women with PCOS and 164 age- and BMI-matched female controls. Circulating betatrophin levels were measured using ELISA. Metabolic and hormonal parameters were also determined. Circulating betatrophin levels were significantly elevated in women with PCOS compared with controls (367.09 ± 55.78 vs. 295.65 ± 48.97 pg/ml, P < 0.001). Betatrophin levels were positively correlated with insulin resistance marker homeostasis model assessment of insulin resistance (HOMA-IR), free-testosterone, high-sensitivity C-reactive protein (hs-CRP), atherogenic lipid profiles, and BMI in PCOS. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.51 for patients in the highest quartile of betatrophin compared with those in the lowest quartile (95 % CI 1.31-4.81, P = 0.006). Multivariate regression analyses showed that HOMA-IR, hs-CRP, and free-testosterone were independent factors influencing serum betatrophin levels. Betatrophin levels were increased in women with PCOS and were associated with insulin resistance, hs-CRP, and free-testosterone in these patients. Elevated betatrophin levels were found to increase the odds of having PCOS. Further research is needed to elucidate the physiologic and pathologic significance of our findings.

Increased circulating urocortin-3 levels is associated with polycystic ovary syndrome.

This study was aimed to compare serum urocortin-3 (UCN3) levels in women with polycystic ovary syndrome (PCOS) and healthy women, and establish what role UCN3 levels play in PCOS. Fifty-two patients with PCOS and 55 healthy women were included in the study, matched for age and body mass index. Fasting blood glucose (FBG), insulin, hs-CRP, UCN3 and free-testosterone levels of the all participants were measured. HOMA-IR was used to calculate the insulin resistance. Circulating UCN3 levels were significantly increased in women with PCOS than in control subjects (54.49 ± 5.77 versus 51.28 ± 5.86 pmol/l, p = 0.005). Serum insulin, hs-CRP and HOMA-IR levels were higher in women with PCOS than in control group. UCN3 levels positively correlated with hs-CRP in PCOS group (r = 0.391, p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curves were 0.732 (95% CI 0.634-0.830, p < 0.001) for UCN3 levels. The optimal cut-off value of UCN3 for detecting PCOS was ≥51.46 pmol/l, at which the sensitivity was 75% and specificity was 68%. Our results suggest that there is a potential link between PCOS and UCN3 levels. The results of this study support the presence of increased UCN3 levels for the association of inflammation with PCOS.

Polycystic ovary syndrome is associated with increased osteopontin levels.

OBJECTIVE: Osteopontin (OPN) is a multi-functional secreted glycoprotein that plays a crucial role in glucose metabolism and inflammatory process. Growing evidence suggests that there is a link between OPN and ovarian function. However, no such link has yet been found for OPN in polycystic ovary syndrome (PCOS). Our aim was to ascertain whether circulating OPN levels are altered in women with PCOS and to determine whether OPN levels differ between the follicular phase and mid-cycle of the menstrual cycle in eumenorrheic women. DESIGN AND METHODS: In total, 150 women with PCOS and 150 age- and BMI-matched controls without PCOS were recruited for this prospective observational study. OPN levels were measured using ELISA. Metabolic parameters were also determined. RESULTS: Circulating OPN levels were significantly elevated in PCOS women compared with controls (69.12±31.59  ng/ml vs 42.66±21.28  ng/ml; P<0.001). OPN levels were significantly higher at mid-cycle than in the follicular phase in eumenorrheic women. OPN was positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free testosterone, and high sensitivity C-reactive protein (hs-CRP). Multivariate logistic regression analyses revealed that the odds ratio (OR) for PCOS was 3.64 for patients in the highest quartile of OPN compared with those in the lowest quartile (OR=3.64; 95% CI=2.42-5.57; P=0.011). Our findings indicate that BMI, HOMA-IR, hs-CRP, and free testosterone are independent factors influencing serum OPN levels and that OPN is an independent predictor for HOMA-IR. CONCLUSION: PCOS is associated with increased OPN levels.

Acquired partial lipodystrophy is associated with increased risk for developing metabolic abnormalities.

OBJECTIVE: Acquired partial lipodystrophy (APL) is a rare disorder characterized by progressive selective fat loss. In previous studies, metabolic abnormalities were reported to be relatively rare in APL, whilst they were quite common in other types of lipodystrophy syndromes. METHODS: In this nationwide cohort study, we evaluated 21 Turkish patients with APL who were enrolled in a prospective follow-up protocol. Subjects were investigated for metabolic abnormalities. Fat distribution was assessed by whole body MRI. Hepatic steatosis was evaluated by ultrasound, MRI and MR spectroscopy. Patients with diabetes underwent a mix meal stimulated C-peptide/insulin test to investigate pancreatic beta cell functions. Leptin and adiponectin levels were measured. RESULTS: Fifteen individuals (71.4%) had at least one metabolic abnormality. Six patients (28.6%) had diabetes, 12 (57.1%) hypertrigylceridemia, 10 (47.6%) low HDL cholesterol, and 11 (52.4%) hepatic steatosis. Steatohepatitis was further confirmed in 2 patients with liver biopsy. Anti-GAD was negative in all APL patients with diabetes. APL patients with diabetes had lower leptin and adiponectin levels compared to patients with type 2 diabetes and healthy controls. However, contrary to what we observed in patients with congenital generalized lipodystrophy (CGL), we did not detect consistently very low leptin levels in APL patients. The mix meal test suggested that APL patients with diabetes had a significant amount of functional pancreatic beta cells, and their diabetes was apparently associated with insulin resistance. CONCLUSIONS: Our results show that APL is associated with increased risk for developing metabolic abnormalities. We suggest that close long-term follow-up is required to identify and manage metabolic abnormalities in APL.